Project Summary/Abstract Suicide rates are on the rise, and recent investments in treatment and intervention have done little to turn the tide. While studies have identified cross-sectional predictors of suicidal ideation and behavior (e.g. age, gender, psychiatric diagnosis), the processes that underpin episodic suicide risk ? that is, episodes of suicidal ideation and behavior as they occur in the real world ? remain poorly understood. Neuroimaging studies examining structural and functional alterations present in individuals with suicidal ideation (SI) and behavior (SB) have implicated elements of a fronto-striato-amygdala circuit underlying executive control and emotion processing as conferring suicide risk. This circuit involves key regions of interest (ROIs) including the dorsolateral prefrontal cortex (dlPFC), ventral medial PFC (vmPFC)/orbitofrontal cortex (OFC), and projections to the thalamus, amygdala, hippocampus, caudate, and frontotemporal-striatum. This neural circuit may moderate emotional response through an opponent process model of reactivity to, and regulation of, emotional experiences. Specifically, initial reactivity to emotion involves bottom-up information processing from sensorimotor inputs to the amygdala and, ultimately, to the anterior cingulate cortex (ACC) and associated ROIs. Conversely, regulation of emotional experiences involves top-down information processing, effortful control, higher cognition, and executive functioning, originating in the PFC and associated ROIs. Our team (1R01MH095786), is developing an emotion reactivity translational endophenotype for suicide integrating genetics, psychophysiological monitoring coupled to an emotion reactivity task (i.e. Paced Audio Serial Addition Task), and real-world symptom and experiential sampling via ecological momentary assessment (EMA). Preliminary findings suggest that participants who have made a suicide attempt (SA) show greater anger reactivity during the most stressful part of the PASAT as compared to participants with SI; this response may represent a novel emotion reactivity marker of suicide risk. We believe that an important next step in understanding emotion reactivity in suicide is to examine the fronto-striato-amygdala top-down/bottom-up information-processing model using functional neuroimaging in association with laboratory-based and real-world measures (i.e. ecological momentary assessment) of emotion reactivity and regulation.